Enthalpic and entropic contributions to lipase enantioselectivity

The enantioselective properties of lipases in the kinetic resolution of chiral substrates are conveniently expressed as the enantiomeric ratio, E. It has been stated that E is related to the difference of the Gibbs free energy of activation of the enantioselective reaction steps by RT In E=-Delta Delta G(#)=T Delta Delta S-#-Delta Delta H-#. From the temperature dependence of E we estimated the enthalpic, Delta Delta H-#, and entropic, Delta Delta S-#, contributions. Contrary to earlier suggestions (Aqvist, J. and Warshel, A., 1993. Simulation of enzyme reactions using valence bond force fields and other hybrid quantum/classical approaches. Chem. Rev. 93, 2523-2544.) it is found that the entropic contribution, T Delta Delta S-#, to lipase enantioselectivity at ordinary temperatures is significant. Plots of Delta Delta H-# versus Delta Delta S-# for enzyme-catalyzed kinetic resolutions reported in the literature, show a tempting linear correlation of the enthalpic and entropic contributions. On closer inspection, we realized that this is the result of a non-random selection of systems. Hairpin curves are observed for plots of the enthalpic and entropic contributions to lipase-catalyzed enantioselective reactions in water-cosolvent mixtures and in organic media as a function of medium composition. The importance of these findings for the fundamental understanding of enzyme enantioselectivity, the rationalization of solvent effects on the enantiomeric ratio and the prediction of lipase enantioselectivity by molecular modeling techniques is discussed. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.